Hormone Replacement Therapy with Dr. Felice Gersh: Rational Wellness Podcast 214

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Dr. Felice Gersh speaks about the Hormone Replacement Therapy with Dr. Ben Weitz at the Functional Medicine Discussion Group meeting on June 24, 2021.

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Podcast Highlights

4:28   This discussion is about the use of Hormone Replacement Therapy, which was part of the therapies involved in the protocols used in the first study by Dr. Dale Bredesen and his group on using a Functional Medicine approach for reversing Alzheimer’s Disease. The first paper was just published in preprint showing this:    Women have 2-3 times the incidence of Alzheimer’s Disease.  By incorporating estrogen into these protocols, Dr. Bredesen is providing evidence for the benefits of estrogen for brain health, even in older women starting estrogen at this later age. 

10:51  Dr. Gersh specializes in research and evidence based care but patients really just want to know what are the benefits of care, like taking hormones.  Menopause is really ovarian senescence, which is a gradual process of loss of your eggs and loss of your fertility and loss of your ability to make hormones with the perfect rhythmic patterns that are the menstrual cycle. And the problems that ensue from losing these hormones start early on, including atherosclerotic plaque development in the arteries and inflammation and intimal thickness of the artery walls. Menopause is a process and women can develop a lot of symptoms like mood swings, sleep disturbances, night sweats, hot flashes, and these can occur before a woman completely loses her cycle.  It can be helpful to get a cycle mapping test where you measure their hormones daily for 30 days using urine and you might see that their hormone levels are terribly off. Dr. Gersh prefers to use ZRT Lab, though Precision Analytical offers this dried urine test as well, known as DUTCH testing.

13:57  By doing this mapping of hormone levels throughout the menstrual cycle, you can actually create a personalized precision plan for that patient, which is really what we in Functional Medicine want to do.  Dr. Gersh will often see estrogen levels way below normal and she will prescribe the appropriate amount of bioidentical estrogen and progesterone in a cyclical fashion and women will often feel dramatically better. When women go through menopause, they often have mood changes, depression, anxiety, sleep disorders, along with night sweats and hot flashes.  There are often gut problems/dysbiosis, a pro-inflammatory state, fatty liver, and an overly sympathetic nervous system activation, which can negatively affect your heart.  Because she is using bioidentical hormones, it would not harm a pregnancy if that were to happen. Women who use bioidentical hormones will often see an improvement in both cognition and in mood, which is important since depression and anxiety are very common during this menopausal transition.  Hormones also often improve the sleep problems that are common during menopause.  During the transition a woman’s gut often becomes dysbiotic and they develop leaky gut. Their gut immune system without estrogen tends to default to a pro-inflammatory state with lots of inflammatory cytokines, often triggered by LPS.  And women are prone to develop Takotsubo syndrome, which is also known as broken heart syndrome, which is like a total disruption of the autonomic nervous system, sending these extreme states of sympathetic output to the heart that creates this disruption in the heart that is very similar to a heart attack.  After menopause, women are also prone to get mild diastolic dysfunction, which is basically a stiff heart with deficient amount of energy, and the heart simply doesn’t make enough energy.  This can be a precursor to a form of heart failure that’s kind of unique to women where we call it conserved ejection fraction.  The heart still pumps, but it doesn’t relax properly.  There is a form of heart failure that’s unique to women.

17:08  It is often not appreciated that how much taking hormones will help with mood and cognitive issues. Menopausal women often have sleep problems and hormones can often help with sleep as well. As a woman goes through menopause, her gut becomes dysbiotic and she will tend to develop leaky gut.  Hormones can be very helpful in improving the microbiome. And if you have the wrong microbes in your microbiome, you don’t make enough butyrate, which means that you don’t trigger the parasympathetic nervous system properly.

23:43  Besides the heart, the other organ that requires a lot of energy is the brain and the same process occurs in the brain.  There are microglia in the brain, which are modified macrophages, and they have the capability to make enzymes like matrix metalloproteinases and myeloperoxidase.  These enzymes dissolve invaders, but they are modulated by estradiol and without adequate estradiol, they default into their activated state and they release these enzymes at the least little provocation and they can start dissolving our healthy neural tissue.  Amyloid plaque is created to try to control inflammation in the brain and can increase due to the lack of estrogen. 

28:09  Estrogen is not pro clotting, it’s pro balance.  But this can be a problem for oral forms of estrogen, which go through the liver and get converted into estrone, which works predominantly on the alpha receptor, which is more pro-inflammatory.  The beta receptor, which is anti-inflammatory, is promoted by another form of estrogen, which is estriol.  We need to have a balance of estrogen and our other hormones.

 

 

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Dr. Felice Gersh is a board certified OBGYN and she is also fellowship-trained in Integrative Medicine. Dr. Gersh is the Director of the Integrative Medical Group of Irvine and she specializes in hormonal management. Her website is IntegrativeMGI.com, and she is available to see patients at 949-753-7475.  Dr. Gersh lectures around the world, and she has written two books, PCOS SOS: A Gynecologist’s Lifeline to Restoring Your Rhythms, Hormones, and Happiness and PCOS Fertility Fast Track and she has recently published a paper in the prestigious journal Heart, which is part of the British Medical Journal family of journals: Postmenopausal Hormone Therapy for Cardiovascular Health: the Evolving Data.

Dr. Ben Weitz is available for nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.

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Podcast Transcript

Dr. Weitz:                            Hey, this is Dr. Ben Weitz host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates and to learn more, check out my website, drweitz.com. Thanks for joining me. And let’s jump into the podcast. Welcome everyone and thank you for joining our functional medicine discussion group meeting. I’m Dr. Ben Weitz and our topic for tonight is hormone replacement therapy in post-menopausal women with our special guests, Dr. Felice Gersh. I’ll start by introducing our sponsor for this evening, which is Integrative Therapeutics. So, now I’d like to introduce my friend, Steve Schneider from Integrative Therapeutics to tell us a little bit about Integrative and their professional line of supplements, Steve.

Steve:                                  Can you hear me?

Dr. Weitz:                            Yes, we can.

Steve:                                  Yeah. So, thanks again Dr. Weitz for letting us sponsor, we’re excited. I can tell you that HRT is not our area of expertise. So, I’m going to learn a lot tonight. That being said supplement wise, there are a few products that we get asked about a lot in this area. Changes to the body’s natural fluctuating levels of estrogen through either menopause or surgical menopause have been linked to cognitive issues and there’s growing sort of consensus that this is related to inflammation. So, that’s where our Theracurmin comes in. It’s generally considered to have the unsurpassed bioavailability and provides super high blood and tissue levels. Among the numerous clinical studies, there was one recently done at UCLA showing improved memory and mood with using just the two caps per day. They also did scans and saw decreased amyloid tangles and tau proteins in that study. And then kind of on the same-

Dr. Weitz:                            And there was no bleeding in the brain.

Steve:                                  Exactly.

Dr. Weitz:                            That was just approved.

Steve:                                  Right. And then on the same kind of inflammation under nine cognitive guideline decline, we have a product called Neurologix. That one has studied doses of saffron, spearmint, and citicoline, all that have been shown to improve working memory, sustained attention, focus, and mood. So, that’s a pretty cool one. And then lastly, we know that menopause can cause the incidents of metabolic syndrome, including potential increases in insulin resistance and changes in lipid concentrations and especially surgical menopause is challenging in this area. So, these are kind of the candidates that we’ll be hearing about tonight. And Berberine is the product that we have that has been consistently shown to have positive impacts on these markers. We use a purified Berberine, that’s the study dose at a price that’s typically about $10 less than the brands that I won’t name tonight. And it’s not a gross extract of Berberine like you typically see in an anti-microbial formula of Berberine. This is the pure stuff that they use for the metabolic study. So, that’s all. And have fun tonight. Thanks.

Dr. Weitz:                            Thank you Steve. Okay. So, now Dr. Gersh I’m going to share my screen. I’m going to play the video and then right afterwards, she’s going to call in for Q and A. Dr. Gersh, thank you so much for joining us today.

Dr. Gersh:                           Well it’s my pleasure. And I’m happy to say that from a virtual perspective, I have been touring the world this last year. This past weekend, I spoke to a group in both Ireland and in Australia. So, at least the COVID pandemic has not stopped the interest in learning and Integrative Medicine, I think has grown more interesting to a lot of doctors as they’ve looked for alternative ways to stay healthy. And that’s sort of been my path is looking sort of off the beaten path as to what can women do to optimize their health in this world that we live in, which is so complex.

Dr. Weitz:                            Yes, absolutely. And it’s really interesting just earlier today, I interviewed Dr. Toups and she is part of a group that just conducted and completed the first study that found that Alzheimer’s disease could be reversed using a functional medicine approach. This is using essentially Dale Bredesen’s approach and they published the first paper in pre-print. And this is interesting because he comes on the heels of this new drug, the first new drug that was approved by the FDA for Alzheimer’s in, I don’t know, like 12 or 15 years. And yeah, it turns out that this drug does not make a single patient better. Nobody gets better with this drug. It only costs $56,000 a year and somewhere between 20% and 40% of the patients experienced either swelling or bleeding of their brain and only a small percentage of the patients only after they shifted through the data and reanalyzed it, even experienced the slowing of their Alzheimer’s disease.  So, here we have $400 billion dollars spent on drugs that have failed to actually reverse Alzheimer’s disease. And now we have very exciting research in his study that was published that showed a reversal of Alzheimer’s disease, but using a functional medicine approach. And of course, part of that approach involved giving these patients hormones.

Dr. Gersh:                           Well I’m so glad I was just going to chime in with the hormone aspect of brain health. And my paper that was published as in BMJ heart, so of course the focus is on cardiovascular health but I talk all the time about the importance of hormones, particularly estradiol but also testosterone, progesterone for the health and maintenance of cognitive wellness. And that is so critical. That’s why I’m very excited that Dale Bredesen and his group incorporate the use of estrogen in their treatments and in the form of estradiol from using it topically. So, that’s really important and I definitely think that reversing early cognitive decline and earlier Alzheimer’s, it’s really hard. Any late stage disease, end stage disease is kind of hard. Like go try to reverse someone who’s in massive heart failure or they’re about to go on dialysis or older bones or if they’ve had multiple fractures from osteoporosis.

So, we don’t have great ways to deal with end-stage disease at any point, but we do have amazing things that we can do when we’re in the early stage or my favorite is total prevention. And in terms of like Alzheimer’s, we know that almost three times the patients dealing with Alzheimer’s are females and this is age matched. People say, “well that’s because women live longer”, but we’re talking about age match men and women, that women have between two to three times the incidence of Alzheimer’s disease. And they also have significant rates of vascular dementia because vascular disease, getting back to the article I published is unfortunately highly prevalent in post-menopausal women.  So, you have to think about well, let’s try to be proactive. Like I love that you brought up the cost of that drug. That is an insane cost for a drug that is not beneficial. I mean it would be bad if it was great, but well look at the savings that you’re keeping people out of long-term care facilities, all these memory centers that are basically unfortunately housing dementia patients, because we know that they’re not exactly incorporating Bredesen’s protocol. So, basically it’s predominantly housing and just caretaking, that’s not much of anything else.

Dr. Weitz:                           Yeah. No. There’s absolutely no protocols in those houses.

Dr. Gersh:                           No. And they’re extraordinarily expensive. They can cost $20,000 a month.  I mean so you’ve got to be really wealthy to be put in one of those places. I start saving now for your memory home experience.  But my goal is to keep every person out of those homes and not even have to do like a Dale Bredesen protocol.  I’m into total prevention, that is the best treatment as an ounce of prevention is worth a pound of cure. So, that’s where the whole hormone picture comes in.  And I know that there are some out there that loves the idea. And I understand the appeal that menopause is a beautiful time in a woman’s life when suddenly she’s free of the burden of worrying about contraception and truthfully that’s the only silver lining that I could find.  And I tried to make a list of all the pros and cons.  And that’s the only one if that if you don’t want to be pregnant, then you’d never have to worry about it again when you no longer have any fertility capability.

Dr. Weitz:                           Well I’m sure there’s a lot of other positives. Another positive is you don’t have to worry about a period.

Dr. Gersh:                           But you don’t have to buy tampons.

Dr. Weitz:                           Exactly.

Dr. Gersh:                           Well not if you’re my patient though because here’s the thing. Well of course you don’t have to do. I don’t force my patients to do anything. My role is as a medical consultant, right?  I provide information and support and patients make their own choice.  So, I think of myself kind of like the very friendly waiter at the restaurant.  So, I say, :okay, here are the specials for today. I highly recommend this one. I think you’ll love it.” But that doesn’t mean as the customer, you have to choose it.  You can say, “no, I’ll take the Cobb salad. I don’t want your specialty stroganoff”.  And my patients sometimes say, “no thanks Dr. Gersh. I don’t want your hormone special of the day.”  I just want to work with natural-

Dr. Weitz:                           What wine do you recommend with the estradiol?

Dr. Gersh:                           Well here’s the thing, I specialize in research and evidence-based care therapy. So, every time I recommend something I can give you like laundry lists of why you should do it. Of course, most people don’t even want to hear all the why’s. They just want to hear all the benefits in terms of like, what happens if you don’t do it, they don’t want to know.  They want to know what are you going to get for me?  Everyone wants to know what’s in it for me, which is totally what a doctor is supposed to do for a patient is to make sure they get the optimal choice for them as best as possible.  So, the reality is first, if you look at the data and we have a ton of data on what happens when you don’t have estrogen and a little bit on progesterone.  Progesterone has sort of been the forgotten stepchild of the sex hormones, but that’s a whole separate thing.  And I am really very much in favor of progesterone. That’s why even in women who have had a hysterectomy, I recommend that they incorporate progesterone, not a progestin, not a phony baloney mimic, but the real thing–progesterone–in their therapeutic protocol with hormones. But in terms of what happens when you don’t have your hormones, like after what we call menopause, which is really ovarian senescence, which is a gradual process of loss of your eggs and loss of your fertility and loss of your ability to make hormones with the perfect rhythmic patterns that are the menstrual cycles. So, we have to stop thinking of going into menopause as you’re crossing a finish line. It’s a process and the arbitrary definition of 12 months without a spontaneous period, is exactly that it’s arbitrary. It’s a process of losing your ability to make hormones with the proper amounts, the balance, and the rhythms. And so, the problems that are that ensue from losing these hormones and these rhythms, which is a really key part of it really start early on.

So, we now know that, for example, in terms of cardiovascular health, that atherosclerosis plaque development in the artery and the intimal thickness starts to change. So, you have inflammation of the lining, the intima of arteries and that starts years before actual official menopause occurs. So, this is a process and we need to be aware as well that women may develop a lot of the symptoms of menopause like mood swings, sleep disturbances, night sweats, hot flashes, and they can occur while a woman is still having a regular cycle. And that’s what’s so interesting. A lot of times I’ll get a menstrual mapping test where I can actually see what hormones are producing throughout the cycle. And even though they’re having cycles, their hormone levels are terribly off. They’re not making estrogen or progesterone in the right amounts. And often their LH, which is also measured is like crazy all over the place. And maybe there’s like a little bump and that sort of triggers the production of a little bit of progesterone and then they bleed, but it’s not normal.

Dr. Weitz:                           Who do you do the cycle mapping through? Do you use the Dutch Labs?

Dr. Gersh:                           Well actually I use ZRT. And there are a number of companies, but that’s the one that I have gotten used to and like. You know how we all get set with something and I really like it and it’s very educational. And in fact, I have a whole group and I could do another talk some day if people find this interesting, of a whole collection of menstrual mappings that I’ve done. And I’ve put all the symptoms of the patients together with the menstrual mapping and based on the menstrual mapping and looking at the hormone levels that are occurring during the menstrual cycle, you can really see how it correlates with the symptoms that they’re experiencing.  And then you can actually create a personalized precision plan for that patient, which is really what we in functional medicine want to do. We don’t want to be cookie cutter protocol driven. We want to be precision personalized driven, so each patient is recognized for the unique person that he or she is. And then you can tailor a treatment plan to what that person really needs to be optimized for their health and their future. And that’s what we can do that way.

Dr. Weitz:                           Through ZRT, is this urine testing or is this like-

Dr. Gersh:                           Yeah, so it’s urine. Right. Right. So, and what I’m seeing is like crazy hormone patterns in these perimenopausal women, which really does sync with many of their symptoms because once you understand that hormones are really the communication, now there are other communication systems, but this is the dominant communication system in the body for delivering information from the brain throughout the body. When we’re talking about the standard endocrine system where we’re working through the pituitary gland as sort of the, we’ll say, the master assistant to the brain in terms of distributing information. And that’s why we have these accesses. That’s why they all link together. And you have the adrenal, the ovarian, the pituitary, all these accesses, so that they link together. That’s why when a woman has a great deal of stress, it affects her ovarian function and so forth. So, these all link together. So, and of course, when you-

Dr. Weitz:                           What do you often see on the cycle mapping that correlates with the hot flashes and other symptoms?

Dr. Gersh:                           That the estrogen levels are way below the normal levels, that they’re really low. And it’s amazing because we have a range of everyone who has a menstrual cycle doesn’t actually make the exact same amount of estrogen on the specific day of the cycle. There’s always this deviation, this reference range, right? So, there’s a reference range for that as well. But they’re at the very bottom of the reference range in terms of their estrogen production and it’s really very dramatic how they benefit from a little supplemental estrogen. And you’re not giving amounts that are going to suppress the ovarian pituitary hypothalamic access. So, you’re not shutting things down. It’s not birth control pills. In fact, it’d be nice if that could be used for fertility control purposes, but it doesn’t work. So, if you’re fertile you can get pregnant.

The good news is you’re giving a bio-identical hormone, which wouldn’t harm a pregnancy if that happened. But women feel sometimes so dramatically better. What’s not often appreciated is in terms of mental health because you started with talking about cognition and cognitive wellbeing. Well there’s a complete interaction, interlinkage between mood issues and cognitive issues. That’s why for example, people have Alzheimer’s disease will always have mood problems. They go together and women who’ve had, especially women who’ve previously had any kind of problem with mood, depression, and anxiety, which we know females have far more of this than males. Males have it too but women surpass men in terms of mood disorders like depression and anxiety, that they develop more mood and anxiety, depression problems to the tune of a 400% increase rate from before they went through this transition.  So, it’s not a little thing. Women have a great many emotional problems and then sleep problems dramatically increase as they get into menopause with a lot of sleep, disturbed breathing, sleep apnea, and problems with the phases of sleep. As well of course, night sweats and hot flashes are very disruptive, but even taking them out of the picture, there was a lot of disruptive sleep, which we know links to everything bad. Increase in metabolic functions, insulin resistance, and so forth.  Increase in different cancers when you have poor quality sleep.  So, it’s like a snowball effect of all of these metabolic problems. As soon as a woman goes through menopause, her gut becomes dysbiotic and we have studies on looking at the microbial populations of the gut microbes before and after the menopausal transition.  And there’s a dramatic transition to a dysbiotic gut microbiome and the development of impaired gut barrier or leaky gut goes really high.

And because there are estrogen receptors on the innate, on all the immune cells. And if we talk about the innate immune cells, the mast cells, the macrophages, and the neutrophils, and so on without adequate estradiol balance, they go to their default state. The default state is the pro-inflammatory state. And so, they have a lowered threshold to trigger the release of inflammatory cytokines. So, when you have the lipopolysaccharides, these endotoxins leaking from this dysbiotic gut microbiome into the surrounding gut lymphoid tissue where you have all these immune cells lined up ready to deal with whatever comes their way, they explode with inflammatory cytokine production. And the whole thing is just such a mess. And when you don’t have the right short chain fatty acids, you don’t have the right signaling to the liver. And then you have this inflamed disrupted liver. And then there’s very high rates of fatty liver in women after menopause.

And of course the vagus nerve that big finger of the brain that controls the parasympathetic nervous system has receptors to butyrate, one of the short chain fatty acids. So, when you have the wrong microbes and you don’t make enough butyrate, you don’t have proper triggering of the parasympathetic system. And women, especially after menopause, have a tremendous predominance of the sympathetic over the parasympathetic.  So, they’re way more stressed out and they’re more prone to what is called Takotsubo syndrome, which is also known as broken heart syndrome, which is like a total disruption of the autonomic nervous system, sending these extreme states of sympathetic output to the heart that creates this disruption in the heart that is very similar to a heart attack. And there’s a transient, assuming the person lives and some die, a transient state of heart failure from this overload of sympathetic output to the heart.  And that occurs 90% of the time in women who are post-menopausal. And what’s interesting is I looked into this with cardiology friends of mine, the incidence of this broken heart syndrome, Takotsubo, dramatically increased like 10 times the normal incidents during the pandemic because of the emotional stress that just exacerbated the whole autonomic disruption and imbalance. So, women are definitely different from men. I always like to emphasize, for example, the female heart, which has estrogen receptors throughout. Not only estrogen receptors, what are called estrogen related receptors. So, we don’t know what binds with the receptor, which the binding thing is called a ligand. We haven’t identified it. They used to call them orphan receptors. Now they call them estrogen related receptors, plus whatever it is that binds to the receptor, it doesn’t bind and it doesn’t work unless you have estrogen present like as a co-factor. Just like a co-enzyme will make the enzyme function properly, without estradiol present this process with this other binding element won’t work properly.

And in addition, estradiol metabolites like 2-Methoxyestradiol, which is one of the breakdown products or metabolites of estradiol actually has its own receptors on the mitochondria of the heart and in the heart to increase energy production. So, after menopause when you don’t have adequate estradiol present, there is a very common process that occurs in the female heart that’s called mild diastolic dysfunction. So, what that is basically it’s a stiff heart with deficient amount of energy, the heart simply doesn’t make enough energy. And so, it becomes stiffer and you see it on an echocardiogram that the heart doesn’t relax properly. So, the heart it contracts and it relaxes and the contraction part is still fine. But the relaxing part, you can see the heart is opening and relaxing in a sort of a stiffer way. And that can be a precursor to a form of heart failure that’s kind of unique to women where we call it conserved ejection fraction.

So, the heart still pumps, but it doesn’t relax properly. And that formed a type of heart failure that’s quite unique to females that is very related to estrogen deficiency and you can get an echocardiogram like I do on women as they’re going through menopause and you can actually easily see this. And that’s telling you, it’s yelling at you that this heart is not making energy properly and it’s energy deficient. And of course, what other structure in the body has key need for energy, dramatic nature energy. And of course, it’s the brain. Exactly. So, the same processes are occurring in the brain and in the brain there’s even this extra problem because the immune system of the brain, which has these modified macrophages called microglia, act the same way as the immune cells that line the gut. They’re now kind of like weapons of mass destruction without control because without the proper estradiol, they go into their default state of being pro-inflammatory and they once again will release these macrophages, these microglia are filled with the capability to make these enzymes that dissolve like matrix metalloproteinases and myeloperoxidase.

All these enzymes that are designed to dissolve invaders, like bacteria viruses that get into the brain or to deal with damaged tissue like if you have traumatic brain injury to try to dissolve the damaged tissue and then let the brain heal itself and estradiol modulates these special cells, these microglia. So, they have two states like sort of the surveillance state and the activated state. Without adequate estradiol, they default into their activated state and they release these enzymes at the least little provocation and they can start dissolving our healthy neural tissue. And then now we believe that what is happening in Alzheimer’s is not that the amyloid plaque, this plaque stuff that forms that this new crazy drug is supposed to prevent, that is not the problem. That is the reaction to the problem. It’s when you have the damage and then the body is trying to control it. So, this amyloid beta stuff that’s made is really the body’s trying to deal with this explosion of inflammation in the brain that’s causing destruction of neurons and such. So, that is not going to-

Dr. Weitz:                            What happens in the heart? The atherosclerotic plaque, which is the body’s way to coat the artery against inflammation and oxidation in the artery walls.

Dr. Gersh:                           I love it when we try to understand that everything in the body is designed for survival and fertility. And they sort of go together because if you’re dead, you’re not going to be very fertile, right? So, it’s all this intertwining of these processes of the immune system and it’s amazing. The more you learn about the immune system, the more you’re in awe of it, how it is designed to keep us alive in spite of when we’re starving, when we’re injured, when we’re infected with pathogens, but when things are not properly controlled through hormones and the signaling and it’s not just hormones and it’s related to hormones, but it’s like the whole new world of lipid mediators and all these lipid signaling agents. And what most people don’t know is that these critical lipid mediators, which include the endocannabinoids and especially pro-resolving mediators.

Resolving mediators, especially pro-resolving mediators that include things like the Resolvins that act to help resolve inflammation. So the body has the… Everything is Yin Yang, I don’t know how the Chinese were so smart, but they sure were thousands of years ago that everything is in balance. The whole RAS system, the renin-angiotensin system until recently, relatively recently, we only knew about that the pro-inflammatory arm of this whole very elaborate system, now we know there’s an entire anti-inflammatory balancing arm of this system. Everything in the body has the pro, the con, the hot, the cold and what happens is, when you have the proper sex hormones, like estrogen and progesterone and the proper forms, and in the proper rhythms, it actually balances all of these systems in the immune system. So that you have, for example, estradiol is very key to the initiation of the inflammatory process when it is appropriate, and then it is also key to creating the stimuli to resolving the inflammation, stopping it, and then promoting healing.

That’s why estrogen is not pro clotting, it’s pro balance. And it’s only when you have an imbalance, like you put in a birth control pill or an oral estrogen, that’s why I speak against oral estrogens, because they go through the liver and they get turned into estrone. Now you say “Well estrogen is natural.” Well, yes, but when it’s not in the proper balance, it’s a mess because estrone works predominantly on the alpha receptor, estradiol is balance for all the three receptors that involve estrogen, and estriol, which is the predominant estrogen produced by the placenta in pregnancy is predominantly beta. And they each create their own very unique effects and the receptors actually interact with each other. So if you have a lot of stimuli to the beta, it actually down-regulates the alpha receptor.

And they’re all very critical and they’re in different quantities distributed throughout the body. So different organs have a predominance of one or the other. For example, the innate immune system is predominantly alpha. So you’re mast cells, neutrophils, macrophages, they are alpha. So if all you have is estrone, then it’s like your imbalanced. Now, you’re actually promoting inflammation. Now, if all you have is estriol, that’s beta, beta down-regulates alpha, then that sounds great. Now you’re anti-inflammatory, but that’s not a balance because like in pregnancy they make it so that the innate immune cells… Nature makes it so that the immune cells won’t attack the fetus. But the price for that is that pregnant women are more at risk of morbidity and mortality from infectious agents that get into them.

So there’s a balance, that nature has to balance the immune system to prevent it from attacking the fetus, but at the same time to compromise the innate immune system of the female, but what helps to balance it is the extra X chromosome that women have because the extra X chromosome that doesn’t completely deactivate has… Like 15% of the genes stay active throughout the woman’s life on that second X chromosome. And they’re almost all involved with immune function.

So the female has this backup, even when she’s pregnant, of this extra X chromosome to help her to deal with infectious agents. But the thing is, in menopause, do you want to give estrone so that you’re activating your innate immune cells all the time so that you create this state of inflammation and by the way, breast cancer is always estrogen receptor alpha. So, that would sort of seem, not logical that you would want to give just tons of estrone. Also, the brain does not like estrone. The brain does not… Like all the… cerebral cortex, the limbic system of the brain, they’re all beta. So it doesn’t like it, it loves estradiol. It does not love it, does not love the estrone. So nature made it so that, you have these different estrogens, but they’re all with different purposes and they all have to balance properly.

Dr. Weitz:                            Let’s talk a little bit about, what type of hormones, starting with estrogen that you recommend, and in what form? And so in the functional medicine world, it’s really common to recommend a topical form of estrogen. And we typically… A lot of practitioners will use the Biest cream, and that will be a combination of estradiol and estriol. And one of the reasons for using the estriol is because the estriol is a weaker estrogen. It’s believed to have a lower potential risk of breast cancer. And so therefore using combination of estradiol, and estriol in fact often with a higher level of estriol, that it’s safer.

Dr. Gersh:                           Well, I understand where that theory came from. And I also know that we don’t have any data to support any of this in terms of the actual real world use. So I have to rely, just like everyone else on what do these hormones actually do in the body? And of course, I would love to have some actual studies on such things as, using something like Biest. And so, once you realize that the estriol is not a weaker estrogen, it is simply a different estrogen. It doesn’t bind to the alpha receptor, it binds to the beta receptor. And so it has a different effect and it’s in very large quantities in pregnancy for very specific reasons involving different things that happened related to being pregnant.

Dr. Weitz:                            Right, because you did say that breast cancer is largely related to the alpha receptor. So now if we’re going to [inaudible 00:33:13] the beta receptor, doesn’t it make sense that, that would be less likely to promote breast cancer?

Dr. Gersh:                           That is not the way to go, and I’ll tell you why. Now, if a woman has breast cancer already… By the way, everything is turned upside down, the genes become expressed differently. You have to talk about… When you have cancer for example, it hijacks the whole mTOR system. And so things are different when you have cancer, it really hijacks and changes how the genes are expressed-

Dr. Weitz:                            What if you had breast cancer 10 years ago?

Dr. Gersh:                           Well, if you had breast cancer 10 years ago, I would consider that person as cured, unless they had metastatic. And I’ll tell you… Here, let me… This is so exciting. I think the information about breast cancer. And so number one, estrogen in the form of estradiol does not cause breast cancer. There is a reason why the vast majority of breast cancer occurs in post-menopausal women, not premenopausal women. When breast cancer does occur in premenopausal women. It’s not because they have hormones it’s because they have endocrine disruptors in them that are interfering with the normal signaling of estrogen. We know, for example, that young women who were sprayed with pesticides, like DDT way back, that that set them up for 20 years later, they were 12 and then 20 years later, when they’re 42, they get premenopausal breast cancer, similar to like what [inaudible 00:34:43] a lot of other things of exposure to [inaudible 00:34:45] and BPA and so on.

So it’s endocrine disruptors that are causing the increase in premenopausal breast cancer. And by the way, unfortunately, that includes oral contraceptives and similars, hormonal contraception, because they are actually endocrine disruptors designed to get rid of women’s natural hormones and rhythms. So they do work effectively to prevent unwanted pregnancies, so I have to give them a definite pass on that, they do achieve their ends, but they do have this unfortunate side effect, that they increase breast cancer. So, everyone has to have informed consent so they can make the proper decision for them, what they want to take and how long they want to take it and what the other options are. In terms of women, so this is what happens, when you have a menstrual cycle, a normal menstrual cycle it’s designed to prevent breast cancer, not give you breast cancer.

So the spike of estradiol that occurs that precedes the LH spike, which then induces ovulation, that estradiol spike, actually up-regulates tumor suppressor genes that actually work to lower your risk of breast cancer. Then when you have the peak of progesterone in the mid-luteal phase, that additionally up-regulates tumor suppressor genes. So you have a double system to try to lower the risk of getting cancers. And they’ve actually done breast biopsies in women when they’re having their period, when they’re shedding. And they found that the breast is shedding as well. You can’t see it cause it’s happening invisibly, but senescent, yucky cells are going through a process of apoptosis, cell suicide, programmed cell suicide. So you’re actually killing off the possibly… To turn into breast cancer cells through having this menstrual cycle. That’s one reason that I’m in the process now of developing… Designing a study that will look at rhythmic hormones, designed to as best as we can, try to actually mimic the menstrual cycle where you actually have these peaks of hormones and not just static because static is not natural, It’s not physiologic.

So if we’re going to give hormones, we should try to replicate the best of nature. And the best of nature means estradiol. So, as I mentioned, estradiol controls inflammation, what triggers breast cancer is chronic inflammation in the breast. And what happens is, if you don’t have estrogen in the body being produced by the ovaries, and you’re not having the proper control of your immune cells and your… Everything in the body becomes, pro-inflammatory, the brain, the bones, the gut, the arteries, everything is pro-inflammatory, including the breasts. So, when you have a lot of inflammation, it up-regulates the enzyme called aromatase, which converts androgens into estrogens. Well, women have circulating androgens in the form of DHEA, DHEA,s which is coming from the adrenal, and they convert into estrone. So when you have a lot of breast inflammation, you up-regulate the production locally, not from the ovary locally of guess what hormone? Estrone.

Okay. So estrone is now being produced locally in the breasts. That’s what causes breast density on mammograms. That’s why they say, if you’re post-menopausal and you have dense breasts, that’s a risk for breast cancer. What is that saying? It’s saying that those breasts are inflamed, there’s inflammation in that breast . And it’s producing a lot of estrogen, which then produces proliferation of the ductal cells. So you have more density because you have proliferation of these ductal cells that are going to look on a mammogram as this whiteout kind of thing. Now, when you have a chronic state of inflammation, you have a predisposition for DNA breakage. So now if you have this chronic inflammation, because we know that cancer is a metabolic disease, we’ve learned that, right? So you have this chronic state of inflammation in the breast. You now have DNA breakage, and these cells retain their estrogen receptor that’s still working for the alpha receptor.

And now you have all this estrogen being produced, which acts as a fuel to the fire, that’s going to promote the growth because estrogen is about nourishing and growth and healing. And it doesn’t recognize that breast cancer is cancer, it just thinks it’s injured tissue and it’s trying to heal it because that’s what we’re programmed to do. So we have the sabotaging of the good estrogen, what it’s supposed to do is help to heal and nourish and so on, and now it’s actually promoting the growth of breast cancer. So what if you gave physiologic levels of estradiol? And you started it and you maintained it through the transition into menopause, the perimenopause. So you never went through this state of chronic inflammation, you maintained a healthy lifestyle, you maintained healthy physiologic levels of estradiol, then you wouldn’t get this inflammation developing in the breast in the first place that underlies the formation of breast cancer.

So, when you give estriol, you’re putting a post-menopausal woman into a compromised immune state where her innate immune cells are now being down-regulated. So she become septic, she’s more likely to die. And there is a role for the alpha receptor, and there’s a role for the beta receptor only estradiol bound… And there’s a jeepers, the membrane receptor only estradiol has the balanced effect on all of these different receptors. So my statement is, we are not smart enough to micromanage estrogen receptors so that we know what we’re doing in the brain, the heart, you name it, any organ. So if you give estradiol, you let the body manage itself. You give all the underlying needs…. Make all the underlying needs of the body met in terms of sleep and diet and fitness. And then you give physiologic levels of estradiol along with pulsed progesterone, not daily progesterone, static progesterone, down-regulates the estradiol receptors. So that’s like you’re putting on the brakes on your estradiol.

Dr. Weitz:                            Okay, so let’s talk specifics. What type of estradiol are you…. Do you recommend batches, do you recommend compounded creams. What do you recommend? And then how do you decide how much? And then what type of testing is effective to actually measure whether that estradiol is getting into the body.

Dr. Gersh:                           So, all fabulous questions because our human bodies were not designed to get our hormones through our skin. That’s for sure. So, number one, I do not ever recommend pellets. Pellets are the antithesis of physiologic. When you put in a pellet… And I have done so many tests of hormone levels on pellet patients, Okay? They have these tremendous, super physiologic levels of the hormone for the first month, and then it starts to come down and eventually it hits like a sweet spot, and then it keeps going down until it’s too low. So, my thing is menopause is natural, but it’s not naturally beneficial. And so if I’m going to go against nature to maintain optimal health, I need to conform with the way the body actually works. And that means giving physiologic hormones with some semblance of a rhythm, because we know that rhythms actually help.

So in terms of the estrogen, I will always use a transdermal form. So a transdermal means it goes to the skin, not a pellet, not an oral pill. Now, in terms of transdermal, all estradiol is the same, It’s estradiol. So everything else is the delivery system, whether it’s a patch, a gel or a cream, it’s all inside, it’s estradiol. So, you really do have to do personalized medicine here. About 5% of people are allergic to the adhesive that’s in the patch. So that would be obviously a negative. And, some women don’t absorb from one of the other forms or whichever. So you really do have to test levels because, even the same woman can absorb differently as she ages the skin, the blood supply, the amount of fat in it, the thickness of the epidermis can change.

So you really do have… It’s always a moving target. So you have to really do each patient, you know, the justice of seeing what works for her, and also what is cost-effective. So if you take a woman who’s 65 and over who’s been on hormones and she wants to stay on. As soon as she hits 65, the insurance companies won’t cover it. So, suddenly the cost can really skyrocket if she’s on a patch or a gel, there’s also a vaginal ring, which is, I think covered by nothing and only comes in two doses. So there are occasional women that will still use the Fem ring, but it’s not too common. So at 65, it sometimes becomes unaffordable for women to continue with the gel or the patches. And then I will go always to a compounded and, then you have to try your best to see how you can get it absorbed.

For a cream, I usually start on the inner thigh. I want to put it in an area that has a little bit more fat to try. And this is not always proven, but to try to give it a little bit more time-release as opposed to putting it on a very thin area of skin like the forearm or behind the knees or the labial area where it’s going to be absorbed much faster. That’s what we think anyway. So, because nature obviously doesn’t give you a bolus of hormone at one moment in the day, and then you’re done, and then it just sort of deteriorates.  So if you optimally do it, we would have… Like we have an insulin pump, we’d have an estradiol pump, so that we could… Because the ovaries puts out estradiol in little pulses all day long with larger pulses in the morning. So obviously we’re doing the best we can. I always tell patients, I’m not giving you a set of 20 five-year-old ovaries, I don’t know how to do it, but we’re going to try to get levels into a physiologic range. So they did studies when the, when the patch first came out-

Dr. Weitz:                            By the way, what is the physiological range? Is 60 year old women’s physiological range different?

Dr. Gersh:                           No. So we want to have the optimal levels of a healthy, 20 something year old. So that would be-

Dr. Weitz:                            So even if a woman’s 70, 80 years old. She should have the hormone levels of a 25 year old?

Dr. Gersh:                           Well, yes. But, it’s not typical to start a woman out of the blue in that age group, okay? So, if a woman starts on hormones during the… Within like 10 years of her onset of menopause, preferably earlier than later, there’s no reason to have her go lower and lower. So, that’s really important, the effect of estrogen is definitely dose-related. This whole idea of the lowest doses is the safest dose is unfortunately absurd, because it was meant to be friendly and useful, but low levels of estradiol are actually pro-inflammatory and high levels are the most anti-inflammatory. So you shouldn’t be really afraid, and also by the way, estradiol down-regulates its own receptors. So, if the level gets too high, it will start down-regulating its own receptors. That doesn’t mean I want people to mega dose people, of course that’s not our goal-

Dr. Weitz:                            So, do serum levels of estradiol, reflect a transdermal administration of estradiol? Is saliva testing better?

Dr. Gersh:                           Well, I look for the data and the data right now… It could change, right now is for the, the serum levels. We have the most research on that, by far the most research on that, and I think it is reasonably reflective. I certainly find that when I up the dose, I find the level goes up, and in the vast majority of cases, there definitely seems to be a correlation between the dose I give and the blood levels I measure. So, I definitely always stay right now with blood and I’ve talked to PhDs and lab, and I know that there’s some definitely different opinions on this, and I’m totally open to change when I see more data for the saliva. So right now I’m going with… And the urine is also valid but, it’s just very tested. When it talks to… When you talk about “Well, what is a level that you’re looking for?” All the data I have is from blood testing, not from anything else.

So, the best data is for… That you want to have a level. And now we were talking about Picograms per mil of estradiol, you want to have it at least at 50. So there’s some data that once you get below 50, you can’t even maintain the bone. It’s going to really start… You’re going to start losing bone. So you want to have a minimum of 50 and probably, you can go higher, but for the average, practitioner a maximum of 150. So that would be the range. Now during a menstrual cycle, during the period-

Dr. Weitz:                            Since we’re on testing, is it also a good idea to do urine testing, so we know how they are metabolizing the estrogen?

Dr. Gersh:                           I have no problem with people getting these tests for how people are metabolizing. I think we still don’t know enough and we don’t measure every single metabolite. So, I used to do that a lot more, and I actually don’t now, because I kind of do the same thing with everybody. I assume that they need help with their detoxification pathways. And, we know detoxification starts in the small intestine with phase one, and then it goes through the liver and then back into the gut, with the estrobolome and so on. So I’m going to do everything I can, regardless of what metabolites show, to optimize the function of every aspect of the gut and the liver. And it’s one of those crazy things that having estradiol in physiologic amounts will help the gut to work better, because the enteric nervous system that’s the neurological system of the gut also has microglia also has receptors to estradiol and progesterone.

So you want to have the proper balance of hormones for proper Paracelsus, because if you don’t have proper Paracelsus, you’re going to end up with cebo and you’re going to end up with all these other bowel problems. So it’s one of those catch 22’s. You can’t really heal the gut if you don’t have the right hormones, but you’re never going… In reproductive age women, you’re not going to usually have the right hormones if you don’t heal the gut. So, that’s why sometimes you have to give some hormone support while you’re doing some of this healing in menopausal women, It’s hormone support forever because their ovaries will never catch on and take over. So I don’t worry unless somebody has like… Are in the middle of really active liver disease.

So, having fatty liver wouldn’t stop me from giving estrogen, I’m going to do that, and I’m going to do all the other things like incorporate, a reset or a detox like most people call it, to up-regulate the detoxification pathways in the liver, support the liver support the gut and also incorporate fasting. Because in terms of resolving fatty liver, there are very few things [inaudible 00:50:37] drugs for fatty liver and fatty liver is very prevalent and fasting all different forms of fasting, including ultimately, multi-day fasting or fasting mimicking diets and so on, combined with time restricted eating and exercise, and exercise tremendously beneficial to resolve fatty liver. So withholding estradiol in physiologic levels is not going to be beneficial and it’s not going to be harmful. It may be beneficial because we know that helping the liver with estrogen is very important that loss of estrogen-

Dr. Weitz:                            So, how do you help deliver with estrogen?

Dr. Gersh:                           Well, by working… You’re going to help the gut because the gut and the entire nervous system and all the intro sites, the lining cells of the gut all have estradiol receptors. And so this can really dramatically improve the health and function of the gut. And we know that when you… And of course the diet, we are always going to give food to nourish and support the microbiome. And we know that there’s this conduit of short chain fatty acids that are formed within the gut that go straight to the liver and then also to the brain. So, when you have an unhealthy liver, it always means you have an unhealthy gut, they’re always bi-directional so we can… And then of course I want to look at environmental toxicants, poor liver is working overtime, if it’s trying to get rid of its own endogenous toxins that we make, that’s what it was designed for predominantly.  And then all those exogenous toxicants that are coming into the body. So I always emphasize trying to live super clean, We want to go organic as much as humanly possible, avoid plastics and pesticides and flame retardants, as much as we can to live a life that’s clean and pure as best we can, water purifiers, air purifiers, and all those things to help, so that you’re not overwhelming the liver with all these other chores that it can’t handle.

Dr. Weitz:                            I Spoke to one doctor who prescribes a lot of hormones, and he told me that every woman, he puts her on hormones, he automatically gives her DIM and he gives her iodine.

Dr. Gersh:                           Well, I start every patient out… I recommend, I can’t force them but I highly recommend that they do what we call a reset, which does involve DIM. Now, I don’t usually use DIM indefinitely, but I do like to use it for at least a month or up to three months and-

Dr. Weitz:                            Sort of like an estrogen detox protocol.

Dr. Gersh:                           Well, I think of it as… It’s for all toxins. So I don’t put estrogen in a separate category of estrogen needs to be detoxified, so does everything else in the body, like all the neuro-transmitters and everything. So, now certainly if I’m going to talk about detoxification, I’m going to talk about it for the Xeno estrogens. We want to get them out of the body. They’re the real poison. We have a lot of fear of the wrong things in our world, people are afraid of estradiol when they should be afraid of BPA [crosstalk 00:53:43] definitely, I want to give them to begin with. And iodine is… I have iodine in all the vitamins that I recommend, I never recommend a vitamin that doesn’t have iodine. I’m not into mega iodine, I do not do mega iodine. I recommend absolutely maximum, would be like one milligram of iodine a day.  … maximum would be like one milligram of iodine a day. That’s like a max dose.

Dr. Weitz:                            Well, that’s actually a pretty high dosage because-

Dr. Gersh:                           That is. That’s a max. I usually…

Dr. Weitz:                            … the average D vitamin has maybe 150 micro-

Dr. Gersh:                           And that’s usually what I recommend. And then, I tell people, “If you like it, you can eat the seafood that has iodine, like wild shrimp and scallops.” This is an expensive menu. You can have some lobster or some crabs, because they have iodine, but you can also have seaweed if you like seaweed, fresh seaweed salad. And that will give you iodine. But I usually don’t go megadose. I mean, that’s like an absolute maximum, if people are doing that.

Dr. Weitz:                            Okay. Environmental estrogens, do they show up anywhere on hormone testing?

Dr. Gersh:                           Which kind of estrogens? The xenoestrogens?

Dr. Weitz:                            Xenoestrogens, yeah.

Dr. Gersh:                           No, they don’t. They don’t. So, you’re not going to… You have to measure them.

Dr. Weitz:                            You’re never going to see a change in any of the… Serum hormone levels are never going to change as a result of xenoestrogen?

Dr. Gersh:                           Oh, you know what? There’s so little data on that. They compete for binding sites. That’s like the biggest problem is that they’re mimics. So they… When you have an endocrine disruptor, they can do so many different things. They can affect the production. So, you’re right. I mean… But we just… They can affect the production of the hormone, the degradation, the elimination, the receptor binding, the distribution, how it gets distributed through the body.  So, everything that affects a hormone can be impacted. But I couldn’t tell you, like if I had a level of BPA, how does that change my estradiol level? I couldn’t… Maybe somebody can. I couldn’t tell you an exact… this ratio or something. But I can tell you that BPA has terrible effects as well on testosterone. I mean, this is like one terrible poison that is in all of us. And…

Dr. Weitz:                            Should we be testing for BPA and other environmental toxins, like doing urine environmental toxin test?

Dr. Gersh:                           You can. Now, the thing with BPA is that, when they’ve done studies on it, they’ve found everybody has it. So, you can assume that you have it in you. Now, BPA is one of those… At least… Although this is also a little controversial, it’s one of those fast in, fast out, relatively. So, what level you have today may be a different level from last week or next week, even if you’re living similar life, just because of the way you get little exposures here or there, like maybe you went to someplace where they had plastic storage of some food, and then you got it more from… So, BPA is considered one of the faster eliminated, but very fast because you’re always exposed to it. So, I just assume everybody has it. I’ve gotten cheap… try to keep costs down.

Dr. Weitz:                            Okay. Let’s get back to your recommendations for hormones. So, women are going to use either a patch or topical estradiol, and then-

Dr. Gersh:                           So, I’m totally flexible. And I ask a woman, What would you like to try first?,” Some of my patients, they have a feeling that compounded is superior. And then I say, “Well, compounded means that the estrogen that’s produced, the estradiol, is produced in a factory, probably the same factory that made the estradiol that went into the patch. But then, it’s shipped to the compounding pharmacy. And the compounding pharmacy then puts it into the delivery method. And it could be a cream. Now, some people are very sensitive.  So, there’s some beautiful things that you can get from compounding pharmacy. They can use products that don’t have the same additives or preservatives that are in some of the commercial products. So, for people who have sensitivities to their skin, they react, or they don’t… They may not absorb. I have patients that simply don’t absorb the estrogen from the patch. It’s terrible. But then, I wonder if maybe these generic patches are not very good too, by the way. That’s the brand that I think are very superior.

Dr. Weitz:                            So, we got the topical estrogen. Then, I want to know what type of progesterone? And do you look at other hormones? Do you recommend a pregnenolone? Do you recommend testosterone? And what form of dose? So, let’s go to progesterone.

Dr. Gersh:                           So, let me… Just one second more. So, with the estradiol for a younger patient, I don’t start low. I mean, so just so you know. Remember, higher levels of the patch or the gel are going to get you more physiologic levels. When these hormone delivery systems were put on the market, it was during the time when everyone was pushing, give the lowest dose possible, the lowest dose possible. So usually, if you go much below the 0.075, or the 0.1 patch, or the comparable for the gel, you’re going to get very low levels. And when they did one of the studies that I talk about in my article that’s in Heart, they used 0.05. And the levels that they got were low. They were like 40 and below. They had some women who had levels that were like 15. And that’s like having nothing.

So, don’t think start low is safe for women who are newly menopausal. Then, in terms of progesterone, the most data we have is on the oral form of the micronized progesterone, which most women tolerate well. And some women say it helps them sleep better. But it does get metabolized into other metabolites. And when we measure progesterone levels, we’re not always getting a clear cut answer.

So, we’re relying a lot on the studies that show that it does give protection to the endometrium and reasonable levels. There are some people that are giving different levels of progesterone. But by and large, I would give 200 milligrams for 14 days. And if a woman is no longer having periods, I would usually say the first 14 days of the month, because it’s just easy to remember. If she’s still having some periods, then I try to take… have her take it for the 14 days before the expected period, if she’s going to be doing it to try to regulate the cycles. But sometimes, she does have cycles. And so-

Dr. Weitz:                            What about your patients who go, “Look. I don’t want to get my period back”?

Dr. Gersh:                           Well, first I explain that when you have post progesterone, like the 14 days for the month, that you’re doing a lot of good things, that there’s data to show that it’s better for the cardiovascular system, for the breast. So, if you’re taking hormones so that you actually are going to have healthy longevity, you might as well take it in the most efficacious way. And the periods are usually very predictable, and not very long, and not… They’re not like… They’re made up periods. They’re induced bleeds. So, they usually are not associated with PMS. There’s no menstrual cramps. They’re not very long. They’re not typically very heavy. So, they’re very mild, we’ll say, and very tolerable. So, I try to push for that.

And I also explained that, if you are on progesterone all the time, you’re continually down-regulating your estrogen receptors, which is why many women, when they’re on continuous estrogen and progesterone, they start having hot flashes again. And they say, “What the heck is this?” It’s because you’ve totally down regulated your estradiol, all of your estrogen receptors. So, that is not very useful. So, most women will go along with it. If they absolutely won’t, then I have to do what they ask me to do. I mean, I don’t have to. I can say I won’t do it, but I think some is still better than none. So, I will then give them an estrogen and progesterone together. But then, I explain as well that estrogen is about growth of the uterine lining, if we just talk about the uterine lining.

Estrogen is about growth or proliferation. And progesterone is more like the breaks, and then sort of flourishing, like flowering. So, you’re giving the body two different information signals. One is to grow. One is to stop. So, it’s like you’re driving the car with the brakes and the gas on at the same time all the time. When you give it pulse, what you’re doing is you’re taking the proliferation of the estradiol, and then you’re saying “stop now”. And then, you go and you become more secretory. And then, you shed, if you’re not, so it’s like natural type of cycle mimicking. But otherwise, you’re trying to grow and not grow at the same time. Now, people think that’s okay because they’re used to birth control pills, which are completely artificial, and will give a progestin and the ethanol estradiol at the same time.

And then, the goal is to atrophy the uterine lining by giving something that doesn’t allow growth. But if you’re going to do that, and be successful that you don’t have a lot of breakthrough bleeding, usually, you have to give a very small amount of estradiol, or else you’re going to get too much proliferation. Then, you’re going to have irregular bleeding all the time, which is worse than having a predicted period. And so, you’re going to have to give a very small amount of estrogen, which is going to be inadequate to do all the things that are going to be needed to keep the body optimally healthy. And then, you’re giving progesterone, but you’re not giving it in a pulsed way, so you’re not going to get the same benefits.

And you’re giving a lower amount, typically. And so, it’s not physiologic. So, there’s nothing physiologic about giving hormones in menopause. I always understand that. Okay. But if you’re going to go against nature, which I’m for… I mean, like I say to every woman, “If you dye your hair, then you’re going against nature. So, why stop there?” You know? Let’s keep going and do everything to look better and feel better.

Dr. Weitz:                            Okay. So, they’re going to take the estrogen and progesterone, and then do… Do you offer and you recommend testosterone?

Dr. Gersh:                           I do.

Dr. Weitz:                            And in what form? And do you ever recommend pregnenolone?

Dr. Gersh:                           So, testosterone. So, testosterone is separate from menopause. It goes down on its own accord. And by age 40, the average woman will have about half the testosterone level she had at age 20. But I get testosterone levels. And I look at the reference range. So, I want the woman to be in the top at least 75%. So, if she’s in the bottom quartile, or the bottom 25%, then she… and she has desire to be on testosterone, then I will give her testosterone.  If she’s having a lot of symptoms and she’s even in the bottom half of the reference range, and she’s having a lot of symptoms, I’ll give her a small amount. I always start low.

Dr. Weitz:                            What kinds of symptoms are you talking about?

Dr. Gersh:                           That she feels that she can’t maintain muscle mass, that she’s having cognitive problems, because testosterone is also involved in that as well. And she’s sort of like lost her vibe. So, she’s lost her motivation. She feels kind of blah. And of course, no sexual interest, no libido. And just feels like that sort of blah feeling, like men get that too, if they have low testosterone. They just like, “I’ll just sit here on the couch and maybe I’ll just go to sleep.” So, it’s like nothing is very interesting. So, it’s okay to give. And I give a small dose. I never start high. I don’t give mega doses. I start with like one milligram.

And then, I follow the levels, because I’m not trying to grow a beard. And it’s amazing how some women are very sensitive. And you make your patients get acne, and they’re like 50, they’re not going to appreciate you. You know? So, it’s better with estradiol to not start low, to start higher. Okay? And you can always… If it’s a patch, you can always cut it. You can always reduce how much you put on. But with testosterone, I always start low, because nothing is worse for a woman than she gets acne and a beard because of your prescription. So, we don’t want to do that.

Dr. Weitz:                            And would you recommend DHEA?

Dr. Gersh:                           I do, if the DHEA level is below a hundred, particularly significantly below a hundred, and she has issues with like a lot of belly fat and insulin resistance. So, there’s… Go to pub med or go to even Google, you’ll see there’s a lot of data on DHEA in women to help insulin sensitivity and reduce visceral fat. You know? So, I don’t… I don’t start all these things at once. I’m very stepwise, because I don’t know, if someone has a side effect, what it’s due to, if I give everything at once.  So, I’m like slow and steady wins the race. So, I start with estrogen progesterone. And I make sure everything is right with that. And then, I will add, typically, the testosterone. I see how they’re doing. And then, maybe I will add the DHEA. Now, in terms of pregnenolone, I measure that on all my patients who feel like they’re highly stressed and just feeling like a lot of brain fog, low energy. And I will often see really low levels, like 10, things like that. And so, then I tell them that this is a sign of chronic stress. Okay? And it’s not that they’re adrenal broke, but they’re really stressed out. And so, this is like a type of a form of adrenal fatigue type of a thing, with this really low pregnenolone.

So, I will sometimes tell them, “I’ll give you pregnenolone. And then, we’ll try to do all the lifestyle things and balance your hormones. And then, we’ll take it away.” So think of it as sort of like training wheels, or like a little crutch, if you broke your leg or something. I don’t want it to be forever. This is just to help you feel better now. And then, I’ll give something like maybe [inaudible 01:07:24] milligrams BID. And then, I will try to wean them off of it over like… after maybe by six months. And I don’t want them to be on it forever.

Dr. Weitz:                            Okay. And, I mean, it’s not harmful though, is it?

Dr. Gersh:                           You know what? Some people… I guess what I’m hoping is that their bodies can do it themselves. If someone… If you take it away or wean it down, and their levels are plummeting, then I don’t have a problem. I don’t see it as something harmful. I guess I’m always trying to get the body to support itself if I can.

Dr. Weitz:                            Of course. And DHEA? Five milligrams? 10 milligrams? Where are you on that?

Dr. Gersh:                           I start low with that as well, because I also don’t want to have androgen excess symptoms, probably because I see so many PCOS women who have really high… But in a lot of the studies, they use 25 and even 50 milligrams. But I don’t start there. Okay. So, I start at five. And then, I’ll say we can up it to 10. And then, I would… I typically don’t go above 25, but there actually are studies published using 50 in women. Usually, when I get up that high, they do have some side effects, so I don’t really want that.

And there’s actually data published that 25 milligrams of DHEA will help maintain ovarian function in women who are perimenopausal, to give them a longer ovarian lifespan. So, I mean, it’s… DHEA needs definitely to be considered, because it’s… In the perimenopause as well, it might help to maintain ovarian function longer, which is actually a very great gift you can give them. If you can get them to have even one extra year of ovarian function is very beneficial.

Dr. Weitz:                            Right. Okay, good. So, I think we covered a lot of stuff.

Dr. Gersh:                           Yes. I think we did. I hope that everyone will think about when they use hormones.

Dr. Weitz:                            So now, time for Q and A. And we’ve got a bunch of questions. Lots and lots of questions actually have come in. Everybody’s been typing them into the chat box. So Dr. Jeanette Ryan wants to know, “With your deep understanding of female health, would you please comment on jab during pregnancy?”

Dr. Gersh:                           Hi, can everyone… Can you hear me okay?

Dr. Weitz:                            Yes. Hi.

Dr. Gersh:                           Great. Great. So, the data is still quite sparse. Unfortunately, there is not a great deal. But what there is, according to the literature, because that’s all I can go by, is they’re saying that there is no higher incidence of any sort of pregnancy complication or loss compared to a non jabbed population. Now, very few pregnant women are actually volunteering, relatively, compared to the number of pregnant women out there. A very small number are actually volunteering to get jabbed. It hasn’t been taken up by large numbers of pregnant women. So, we don’t have humongous amounts of data. And as well, many of the women who have been jabbeded were jabbed in the third trimester.

So, I think that I would never recommend getting jabbed in the first trimester. And right now, the numbers are down. If we actually had a massive growth in the incidence, and we had more safety data, and women couldn’t really isolate themselves, then maybe there could be a value. But right now, the way… especially with the numbers that are out there, and the limited data that’s available, I would hold off on jabbing. But the official data that’s published is saying that there’s no increase in outcomes that are negative in the jabbed women.  Of course, we don’t have long-term data on the babies. There’s zero long-term data on babies. But there’s also… Just to play the fairness thing here, we also have no long-term data on the babies who are actually exposed to the actual infection either. So, we don’t really know what might happen to them either.

Dr. Weitz:                            Dr. Westman wanted to know, “Is there any problem with giving hormone replacement for the rest of the life of a woman?”

Dr. Gersh:                           Happily, you can now do that, which I personally will do for myself. And I do advocate to do that. In 2017, the North American Menopause Society came out with a new position paper. And in their position paper… Excuse me. Can you step aside for just a minute, a little bit? I’m recording. That’s okay. I just asked these nice gentleman to step aside. So anyway… So, the North American Menopause Society, which is a very big, very respected organization, they were very… also very retro in terms of their approach to hormones for so many decades.  And I really disliked their position. But they did finally, in 2017, come out and endorse the use of hormones for the life of the woman, for the following three reasons. And so, this was sort of a very clever, beautiful idea: for menopausal symptom suppression, for bone health, and for quality of life.  So, you now have a major society that actually says that you can do this. And so, now you’re not out there sort of like worried that you’re in no man’s land, that nobody’s going to support you if you have somebody file a complaint against you, which happens like “What the heck are you doing giving hormones to an 85 year old?” Right? Now, you have a major society saying, “It’s okay, as long as you monitor and take care of your patient.”

Dr. Weitz:                            [inaudible 01:13:22]. Are you familiar with bio matrix drop… Wendell asked, “Are you familiar with bio matrix drops, both bio identical, estradiol, and progesterone? Would you use them topically and use both?”

Dr. Gersh:                           Well actually, I need to learn about that particular product. So, what are the doses in it? Does anyone know?

Dr. Weitz:                            Wendell? Did you want to unmute yourself and follow up with the question? Are you there?

Wendell:                              They’re really low. I’m trying to think again, I think it’s around maybe eight milligrams.

Dr. Gersh:                           So, is this an over-the-counter product?

Wendell:                              Practitioner.

Dr. Gersh:                           So, it’s a prescription that you have to write a prescription for?

Wendell:                              No, it’s practitioner. You probably can’t buy this.

Dr. Gersh:                           Okay. Oh, I see. But it’s not… It’s… Right. But it’s sort of like a supplement that sort of expanded, because it’s a hormone. But okay.

Wendell:                              Yeah.

Dr. Gersh:                           So, I don’t actually support that because I want to have levels that are actually physiologic. I don’t want… Now, if all you’re looking for is symptom suppression, then who knows? It might work for symptom suppression. And there’s nothing wrong with symptom suppression. I’d like to have more than that though. I would prefer to have symptom suppression and also better long-term metabolic health throughout all my organ systems, which will not be accomplished by such a low dose that is like a practitioner only.

So, it would not be my first choice, but it might help with suppression of symptoms. It might not be a bad idea, if you have a woman who’s still having regular cycles and is actually having night sweats, hot flashes and such, that maybe that little bit of extra will actually suppress her symptoms while she’s still having regular cycles. So, it’s not… I wouldn’t write it off, but I wouldn’t want to use that as my long-term hormone replacement therapy program.

Dr. Weitz:                            Let’s see. Somebody was asking about the static use of progesterone versus the rhythmic use. I know you’re a big believer. I think you made that pretty clear that the rhythmic use of progesterone is better. I believe that you even think that the rhythmic use of estrogen, in some way, might be more beneficial. Isn’t that correct?

Dr. Gersh:                           Well, yeah. So, it’s important to know that these hormone receptors up and down regulate each other. Estrogen down regulates its own receptor. Progesterone’s receptor is down regulated as well by itself if it’s chronic. So, if you constantly give estrogen and progesterone all the time, you actually start down-regulating the receptors. And especially, estrogen will ultimately have some problems, because progesterone is designed to down-regulate the estrogen receptor. So, you’re going to often have resumption of symptoms. And this is not uncommon that women who are on continuous hormones, both estrogen and progesterone together, that after a number of years, they start… The women start having night sweats, and hot flashes, and don’t feel so well because it’s like tachyphylaxis. The receptors just down regulate.

And there’s also some published data, even going back to the Pepe trial, that showed that rhythmic hormones, when you use the progesterone in a pulsed way, that it actually lowered cardiovascular disease and improved outcomes as well. Ultimately, I… And I’m starting work on a study. So hopefully, we’ll have a study that will show that if you actually do mimic… And this has been around for like 20 so years, but there’s no data for it. If you do mimic a real menstrual cycle as best you can, which is never going to be really the same, but at least sort of close, you actually up regulate tumor suppressor genes when you have the spike of estrogen that precedes the ovulation.

And also, when you have the high level of progesterone in the luteal phase, that also up regulates a tumor suppressor gene. So, nature made it so that the real menstrual cycle reduces your risk of, for example, breast cancer and probably other cancers. So, we know that females have a lower rate of cancers compared to males. But that, of course… That that advantage is lost after menopause.

Dr. Weitz:                            Janet Mandell. She said that she just got… I think she’s thinking about going on hormones, sounds like maybe for the first time. She’s 44 years old. And her estradiol is 496 picograms per milliliter. And her progesterone is point 22 nanograms per milliliter. And her testosterone is 28 nanograms per deciliter. “With estrogen so high compared to progesterone, should I be taking in progesterone?”

Dr. Gersh:                           So, this is like the… really the only time in a woman’s life when she truly can have estrogen dominance, because I always try to talk against that term. But here, when you’re going through the transition into menopause, the slope is down in terms of the production of estradiol, but you have spikes. So, you’re going down, and then you spike up, and then you go down and spike up. So sometimes, you get these really crazy high levels of estradiol. And then, with that, you get really high levels of FSH. That’s why twins are more prevalent in perimenopausal women, because they get these basically super searches of FSH. And in the ovaries that are still capable of making estrogen, you get this explosion of estradiol.

So, one possibility is… And it seems counter intuitive, but you give some estradiol. Now, why would that make sense with such a high level? It’s cause it’s not going to be sustained. And the reason that you get such a high level of estradiol is because the estradiol is less. And then, the brain says, “Hey ovaries, make more estradiol.” So, it puts out the FSH signal and the LH signal to the pituitary, which then puts… Well rather, the brain puts out its little signaling agents to the pituitary, which then puts out these high levels of LH and FSH, which gets the hyper ovulation and the high levels of estradiol. But it’s all happening because the estradiol levels circulating are dropping.

If you can maintain sort of a baseline level of estradiol, then you can actually prevent these crazy surges. So, you will still ultimately go down. But instead of going down with these giant surges, you can just go down more smoothly. This can also help women who get these crazy migraines, these perimenopausal migraines, because they’re having these giant shifts in estradiol. And that really can trigger the worst kinds of menstrual migraines in these perimenopausal women. So, if you give some background estradiol, then… You can even just try an estradiol patch, like 0.05. And then, you’ll just keep these crazy surges from happening. Now, if a woman is still ovulating, then you don’t really have to give progesterone. What you can do is get one of those menstrual mapping tests. And then, you’ll see what kind of progesterone she’s producing during-mapping tests, and then you’ll see what kind of progesterone she’s producing during the cycle. Of course, it’s one cycle. But if she’s having regular periods, she’s probably making progesterone, but maybe not at the moment that you measured it there. That could have been an ovulation, a surge of estradiol. That’s prior to the actual production of progesterone, but getting menstrual mapping really shows you what’s happening in a cycle. But if you have a woman that has crazy high, repetitive high levels of estradiol perimenopausal, think about just putting on a middle strength estradiol patch and see if you can keep her from doing those surging estradiol levels.

Dr. Weitz:                            Now, what about a woman who’s in perimenopause and her progesterone is low and she’s scared to death about taking estrogen? What about her just taking progesterone just to help her with the hot flashes and symptoms? Also, do you think there’s any benefit to chaste berry?

Dr. Gersh:                           Well, actually, in terms of giving progesterone, giving progesterone alone is totally acceptable when you have some estrogen. I would not give progesterone to a woman who makes no estradiol because it’s really like a team. I think of them as like Batman and Robin. You don’t just give progesterone alone with no estradiol. But if she’s making estradiol, but she’s not ovulating, this is typical of my PCOS patients. They’re making some estradiol, but they’re not ovulating, so they don’t make progesterone. And then they have this imbalance of estrogen. They can actually get hyperplasia ultimately and hyperproliferation of their endometrium. And so, you really do want to shed their lining with progesterone. So, there’s nothing wrong with that.

Also, there’s nothing wrong with giving a very small dose of progesterone, say 20 milligrams on a daily basis at bedtime, and that can sometimes help women sleep as they’re transitioning, because that little bit of extra progesterone, it’s not going to change their menstrual cycles. It’s really to help them make more GABA and help them to sleep because they have so many symptoms, and that can also help them to suppress… We know that progesterone can also help suppress some of these nights sweats and hot flashes, so there’s nothing wrong in giving a small dose. I don’t give a high dose. I would start with something very small, like maybe 20 milligrams and see if that will be adequate rather than giving 100, 200 milligrams on a daily basis to a woman, because that’s not… Now, you’re getting way out of physiologic range once you’re doing that.

You can also think about DHEA. So, DHEA has some really interesting data showing that it reduces the production of visceral fat and improves insulin sensitivity in aging women. That can sometimes also help with some of the night sweats and hot flashes. It’s an interesting kind of a hormone that doesn’t always get recognized as having benefit in women.

Dr. Weitz:                            What about pregnenolone, and what is the dosage you like for pregnenolone?

Dr. Gersh:                           Oh, and I forgot. Chaste tree, I use chaste tree a lot. So chaste tree has benefit for a whole variety of things, breast tenderness, PMS, and cramps. So, it may help to promote the production of progesterone. Chaste tree actually has some reasonable published data, so think of it as a first-line choice for women with PMS and with breast tenderness, particularly, but you can try it in perimenopause.

Dr. Weitz:                            What dosage you like for that purpose?

Dr. Gersh:                           About 400 milligrams every morning.

Dr. Weitz:                            Okay.

Dr. Gersh:                           In terms of pregnenolone, so that’s an individual thing. Some people go up much higher than I. So if it’s something mild, in my office, I carry two dose strengths. I carry a 10 milligram and a 30 milligram. So depending on the situation and the level and the patient’s symptoms, I may start as low as 10 milligrams twice a day or I may just start right out at 30 milligrams twice a day, but I don’t generally go… I mean, some people go much higher. I generally don’t. I find that that actually-

Jennifer Lumens:             Hi, Happy.

Dr. Gersh:                           … works fine.

Jennifer Lumens:             Happy. Hi. Hi. Long day, huh?

Speaker 1:                           Yeah.

Jennifer Lumens:             Oh my goodness. [crosstalk 01:25:35].

Dr. Gersh:                           Mute, guys. Mute.

Dr. Weitz:                            Thank you. Jennifer Lumens, please mute yourself. [crosstalk 01:25:45]. Jennifer Lumens, please mute yourself.

Jennifer Lumens:             Oh, sorry. Okay.

Dr. Weitz:                            Okay. Thank you. Somebody was asking a dosage on the patch for the estrogen and they said [crosstalk 01:26:09].

Dr. Gersh:                           If I’m trying to suppress the big spike of estradiol that comes in the perimenopause, I usually start with just a middle of the road dose, like a 0.05, because I’m not trying… This is not a birth control pill. I’m not trying to suppress all of their estrogen production. I’m just trying to help their brain to say, “Hey, I have enough estradiol that I don’t need to put out that gigantic surge of FSH from the pituitary to get the ovary back online.” It’s like such a crazy rollercoaster for women who get this an up and down estradiol. They feel terrible. They get massive breast tenderness, headaches, mood swings. I hate to say it, but it is too much of a good thing.

Dr. Weitz:                            Right. By the way, just out of curiosity, I have a couple of patients in their 70s and they’re still getting hot flashes. How can you get hot flashes in your 70s? What causes that?

Dr. Gersh:                           Well, it’s very interesting. In the brain, we have this thermoregulatory center. All of the hypothalamus is about regulating appetite and temperature. It’s about ovulation. So, it’s the basic functions of the body. It’s really altered when you don’t have estradiol. I actually think it’s amazing that women adjust to it. So to me, the fact that a woman can maintain the… Dealing with night sweats and hot flashes doesn’t really surprise me because there’s nothing really to fix it per se. It’s just an amazing adjustment that so many women make with their bodies that they can actually suppress with no extra estrogen being produced from their ovaries, of course. It’s really a wonderful thing that they can actually suppress the hot flashes and night sweats as time goes by. But it’s something like almost 20% of women will continue to have some nights sweats that are significant and bothersome for almost 20 years. So, it’s actually not an insignificant number of women.

The brain makes estradiol, and that’s the estradiol… The estradiol is a form of estrogen that the brain loves, and it does make it. It makes it from cholesterol from circulating testosterone. So my best guess, because we have no research data on this, is that the brain works very hard, as hard as it can to make as much estradiol as it can after menopause to maintain a healthy brain function. In women who don’t suppress those hot flashes, by the way, that’s an ominous sign. It’s not just misery, having night sweats and hot flashes. That actually is foretelling of increased risk for dementia and cardiovascular events.

So, it’s like the body can’t quite get it to act to make more [inaudible 01:29:04] production or local production of estradiol enough to really suppress the neuroinflammation that’s ongoing in the brain, and then also in the vascular system and in the heart. So, you really want to pay attention to women. So, a lot of things have double meaning. It’s a misery and terrible state for a woman to live with, but it’s also a risk factor, very significant risk factor for ultimately the development of dementia and cardiovascular events.

Dr. Weitz:                            Would you consider putting a 70-year-old woman on a hormone replacement to prevent dementia and cardiovascular disease who has not been on…

Dr. Gersh:                           The conventional medical world would say you’re too late because you’ve gone outside of the so-called window of opportunity as they now label it, and that is 10 years post-menopause, which is, of course, defined as 12 months of no period, but we now have like Dale Bredesen. I love that guy because he is giving estradiol, estrogen to women who have dementia. It doesn’t matter how old they are. So now we have something to support us doing it, because it’s always hard when you’re a maverick, when you’re going outside of the conventional medical world’s recommendations, no matter how bad they are or whatever, but now we can always say, “Well, look, we have Dale Bredesen. He’s published. He’s highly respected. He believes that the neurons of the brain can benefit from the exposure to estradiol at any age.” I remember years ago-

Dr. Weitz:                            I’m sorry, Felice/ you are hereby banned from Facebook now.

Dr. Gersh:                           Oh, that’s true.

Dr. Weitz:                            I’m kidding.

Dr. Gersh:                           I know. But I remember years ago, many years ago when estrogen was still okay, before it went through some bad times with the Women’s Health Initiative that I saw some data. This was all in test tubes, neurons in test tubes. It showed the neurons with and without the presence of estradiol and that vision never left me. With the estradiol, it looked like a rain forest, with branches and leaves and flowers. It looked like amazing these neurons. Without estradiol, it looked like a bunch of dead sticks. So it’s like, “Which brain do I want, a brain that looks like a lush rainforest or dead sticks?” So I said, “I’ll pick the lush rainforest.”

Dr. Weitz:                            So, Telly is asking, “Do you think that estrogen interferes with mold detox pathways?”

Dr. Gersh:                           I don’t. I think it helps facilitate them, because estradiol is very key to maintaining the health of the enterocytes that are in the gut. We know that there’s a strong connection between the health of the gut and the health of the liver, because we know that if you don’t make the proper short-chain fatty acids, which you’re not going to make if you have a dysbiotic microbiome, that you’re going to get an inflammation in the liver. There’s a direct signaling system between… We know propionate and butyrate actually signals from the gut into the liver. So if you want to have optimal liver functioning, you want to have physiologic levels of estradiol. I mean, I don’t know of any data. This is all based on my knowledge of how the body works, that estradiol is going to help facilitate a healthy, functional liver. We know that when you don’t have estradiol, like in menopause, the incidence of fatty liver dramatically rises, and a fatty liver is not a really healthy functional liver that’s going to do a great deal of successful detoxification.

Dr. Weitz:                            We have a question about, let’s see, autoimmune disease. Does that affect your recommendations for a hormone replacement?

Dr. Gersh:                           So in menopause, we know that there’s a significant increase in the incidents, particularly of rheumatoid arthritis. So once again, we know that many new onset autoimmune diseases are related to leaky whatever. So you’re getting microbes that are passing from whatever the entity. It could be the lungs. It could be the vagina. It could be the gut, which often we focus on the gut, but it could be any structure that acts as an interface. You get the wrong microbes, and then they leak into the body and that’s a chronic infection. So, we definitely want to be aware that when you don’t have enough estrogen, you lose all of your healthy microbiomes on the skin, in the vagina, in the gut, in the sinuses. And so, estradiol should help prevent the onset of autoimmune diseases.

Now, there is one autoimmune disease that has certain snips that actually hijack estrogen and that’s lupus. So, there is some data that estrogen can actually aggravate lupus, but when you look at the totality of all the benefits… Because lupus itself has significant risks for cardiovascular disease, so I think that we need to monitor and be very careful with lupus patients. But for other types of autoimmune diseases, estrogen should be very welcomed to help maintain barrier function, and not only barrier function, but immune function, because we know that without estradiol, the innate immune cells become weapons of mass destruction without control. They have a lower threshold to release their inflammatory cytokines and so forth, so we definitely… That’s what all the immune modulators are working on, right? They’re all some kind of cytokine blocker, right? So, estrogen itself helps to control the cytokines. So it’s when you have chronic infections and you have imbalances in hormones that you can often get the autoimmune condition.

It’s interesting. There’s actually some research on multiple sclerosis and the use of estriol, because that is probably the one place, where now not for menopause per se, but as a therapeutic drug, that estriol may actually help because estriol, as a beta receptor agonist, it blinds to the beta receptor. It actually downregulates the alpha receptor, which is what is on the innate immune cells. So it acts as an immune modulator to reduce the inflammatory response of the innate immune cells. So, estriol definitely could be a potential use in women. We just need more data because there’s almost no research on this, but understanding this that for women with autoimmune disease, those are the women that may actually benefit from Bi–est, that I usually speak against, because here, we’re not just giving hormone therapy, we’re actually trying to modulator how the innate immune cells are functioning.

Dr. Weitz:                            Interesting. What about obese women who are over-aromatizing their estradiol?

Dr. Gersh:                           Great question. It turns out that high levels of estradiol downregulates aromatase.

Dr. Weitz:                            Really?

Dr. Gersh:                           Yeah, that’s exactly the truth is the genes that control the enzyme aromatase are downregulated by estradiol. It makes sense. Inflammation causes an upregulation of aromatase. Inflammation in the body causes the body to make more estrogen. Now, in men, if they have testosterone, they’re going to make estradiol. In women, because they’re converting predominantly DHEA or DHEAS are going to make predominantly estrone. So that’s why breast tissue when it’s dense is a sign of inflammation and breast cancer risk because those breasts are full of inflammation and they’re aromatizing like crazy creating all that estrone, which is in causing proliferation of the ducts and then you’re getting the dense breast. But if you have estradiol onboard, if you have physiologic and high normal physiologic levels of estradiol, it downregulates aromatase because the body doesn’t think it needs it. So, it’s a whole new way of understanding aromatase that if you keep women on physiologic levels of estradiol from the perimenopausal transition onward, they will downregulate aromatase. They won’t develop all of these issues, and it should lower their lifetime risk of breast cancer, not increase it.

Dr. Weitz:                            Interesting. Since you just mention dense breasts, what do you think about mammograms?

Dr. Gersh:                           Well, I have very mixed feelings. Okay. Mammograms do save lives, but they don’t save very many lives. They save a very small number of lives. It’s now been shown that about 11% of invasive breast cancers that are found are never going to kill anyone. There was a giant study out of Canada, where they compared women who had mammograms and then women who didn’t, and then they watched them for 30 years and they found the women who had mammograms did not do better. They did not have a lower rate of breast cancer death. Although it didn’t quite meet statistical significance, they actually had a higher rate of all-cause mortality. Now, why would that be? Because women who are diagnosed with breast cancer have some horrendous treatments that are really, really harmful.

They have radiation and radiation is incredibly damaging to the coronary arteries and to the myocardium. This is true, even when it’s on the breasts, that’s on the other side, on the right side. It doesn’t matter. If I was thinking, “Well, at least your breast cancer is on the right side.” No, it turns out the radiation spreads and it hits the heart anyway. Of course, it’s very bad for the lungs too, but especially the heart. Now, I’ve talked to cardiologists who’s done angiograms on women. They say their coronary arteries are frozen. They’re like hard, little, terrible porcelain. They don’t have any flexibility, that it’s really destroying the heart muscle and the vessels. In addition, of course, they get things like aromatase blockers, like letrozole and Arimidex, and then they can’t make estradiol in their brains. They can’t make estradiol anywhere. So, it’s totally devastating their bodies.

They have dramatically increased risk for cardiovascular events. They can’t make estrogen in their arteries. They can’t make it so that they have better bones, so it’s really devastating. So that’s why if you diagnose breast cancer, you may actually have harmed the woman with the treatment, and yet that breast cancer that you diagnosed, even invasive breast cancer, was never designed to kill. We now know that breast cancer doesn’t grow to some magical size, and then suddenly out of the blue, it just metastasizes. It turns out that breast cancer is based on how the genetics are of that breast cancer. They either have cohesiveness or they don’t have cohesiveness. There’s special genes for cohesiveness. By the way, estradiol promotes the gene expression for cohesiveness so that you don’t have breaking off of tissue and then spreading through the body. Estrogen, in the form of estradiol, helps to prevent that. It keeps tissues together.

So, you can have a tiny, tiny little breast cancer that is genetically programmed to be poorly cohesive. It breaks off at a very early stage, and then you already have these metastases. Now, they’re saying the metastases may be dormant for years before they express themselves and start growing, but the die is cast. A woman who is diagnosed with breast cancer, her fate is already sealed, that she’s going to live or she’s going to die based on the qualities of the breast cancer, not the size of the breast cancer. So that whole idea that you just have to catch it when it’s small before it metastasizes, there were gigantic breast cancers that never metastasize and tiny ones that kill. And so, the whole notion of mammography is based on a fallacious premise.

That said, some women will be saved by the mammogram. It will still be found before it metastasizes, but it’s only a small percentage. If you look at breast cancer death, the actual number of breast cancer death per hundred thousand population of women hasn’t really changed. What has changed is that the early diagnosis of breast cancer gives the illusion that they’re living longer because they’re diagnosed earlier. Okay. It doesn’t mean that because they live with it longer, but they still die with it at the same rate. Also, there are many experts that are saying it’s not a one-size-fits-all. If you’ve gone to do mammography, where did this getting it every year come from? That’s made up. So they’re saying, “Look at the woman’s risk. Look at the density. Look at her lifestyle. Look at her body shape.”

One of the biggest risk factors for post-menopausal breast cancer is weight gain and menopause and obesity, which, of course, is metabolic dysfunction. Breast cancer is a metabolic disease. So the bottom line is maybe healthier women who are on hormones, the opposite of what they think, should only have mammograms every few years, not every year. The other thing is breast cancer, it may be occurring due to all the radiation exposure in women in their 40s. It’s setting the stage for them to get breast cancer in their 60. And now that they’re doing all of these so-called 3D mammograms, which are actually CAT scans, they’re low-radiation CAT scans. That’s why they call them 3D, but they don’t want to call them CAT scans. So they actually put out about three times the amount of radiation. So, every woman who has a mammogram from age 40 to 50 will have had three times the amount of radiation in that 10-year span that they would have had they had the old fashioned kind of mammograms.

There’s no proof that the 3D mammograms save lives. The only proof that they have is that they find more insignificant dudettes, so you end up with more unnecessary biopsies. There’s no proof yet that you actually save lives, but you certainly are doing a lot more radiation. So, you can say I’m a little conflicted. But if you don’t recommend a mammogram, you set yourself up for a major lawsuit because that remains the standard of care. So whether your patient has it or not, you better darn well document and actually say, “Would you like a mammogram this year?” and then put it in the note, please, because you will get sued. I’m telling you, if that patient developed breast cancer and she says, “The doctor never told me I should have one,” it doesn’t matter that it would have saved her or not, it’s just you’re going to be in hot water.

Dr. Weitz:                            Awesome. Somebody asked about the cycle mapping. I think I’ll just help answer the question. She wanted to know how would she find out about it. You use A ZRT. The other company that offers the cycle mapping is DUTCH testing. Basically, you’re testing your hormones every day for a month using a little piece of cardboard that you dip into your urine. So, if you want to know about it, contact ZRT and/or contact DUTCH testing.

Dr. Gersh:                           Right. Patients really love it when they see what they’re actually doing in a cycle. Sometimes you’ll be so surprised what they’re doing. It’s amazing, but you’ll learn.

Dr. Weitz:                            Awesome. Thank you so much, Dr. Gersh. This was an amazing [crosstalk 01:45:14].

Dr. Gersh:                           Well, thank you. Thank you for letting me prerecord so that I was able to have dinner and then come back. So, thank you. Thank you so much.

Dr. Weitz:                            Thank you, everybody, for joining us. We’ll see you next month.

 

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Dr. Weitz:                          Thank you, listeners, for making it all the way through this episode of the Rational Wellness Podcast. Please take a few minutes and go to Apple Podcasts and give us a five-star ratings and review. That would really help us so more people can find us in their listing of health podcasts. I’d also like to let everybody know that I now have a few openings for new clients for nutritional consultations. If you’re interested, please call my office in Santa Monica at 310-395-3111. That’s 310-395-3111. Take one of the few openings we have now for a individual consultation for nutrition with Dr. Ben Weitz. Thank you and see you next week.